Appendix 1. Standard search methods

MEDLINE: ((infant, newborn[MeSH] OR newborn OR neonate OR neonatal OR premature OR low birth weight OR VLBW OR LBW or infan* or neonat*) AND (randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab] OR trial [tiab] OR groups [tiab]) NOT (animals [mh] NOT humans [mh]))

Appendix 2. Risk of bias tool

We used the 'Risk of bias' table, which addresses the following questions.

Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated? For each included study, we categorised the method used to generate the allocation sequence as low risk (any truly random process, e.g. random number table; computer random number generator); unclear risk; or high risk (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number).

Allocation concealment (checking for possible selection bias). Was allocation adequately concealed? For each included study, we categorised the method used to conceal the allocation sequence as low risk (e.g. telephone or central randomisation; consecutively numbered, sealed, opaque envelopes); unclear risk; or high risk (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth).

Blinding (checking for possible performance bias). Was knowledge of the allocated intervention adequately prevented during the study, at study entry, or at the time of outcome assessment? For each included study, we categorised the methods used to blind study participants and personnel from knowledge of which intervention a participant received. We assessed blinding separately for different outcomes or classes of outcomes. We categorised the methods as low risk, high risk, or unclear risk for participants; low risk, high risk, or unclear risk for outcome assessors; low risk, high risk, or unclear risk for personnel.

Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed? For each included study, we described the completeness of data including attrition and exclusions from the analysis. We also noted reasons for attrition and exclusions if possible. We categorised the methods as low risk (< 20% missing data); unclear risk; or high risk (≥ 20% missing data).

Selective reporting bias. Were reports of the study free of suggestion of selective outcome reporting? We planned to contact study authors, asking them to provide missing outcome data, when we suspected reporting bias. For each included study, we planned to describe how we investigated the possibility of selective outcome reporting bias. We planned to assess the methods as low risk (when it is clear that all of the study's prespecified outcomes and all expected outcomes of interest to the review have been reported); unclear risk; or high risk (when not all of the study's prespecified outcomes have been reported).

Other sources of bias. Was the study apparently free of other problems that could put it at high risk of bias? For each included study, we described any important concerns we had about other possible sources of bias (e.g. whether a potential source of bias was related to the specific study design, whether the trial was stopped early owing to some data‐dependent process). We also assessed whether each study was free of other problems that could put it at risk of bias as low risk; unclear risk; or high risk.